The following studies concerned with the mechanism of phosphoryl transfer are in progress: 1) stereochemical studies involving chiral phosphorothioate substrates to probe the overall stereochemistry of the reactions catalyzed by bovine intestinal enzyme (5'-phosphodiesterase) and spleen phosphodiesterase (3'-phosphodiesterase); 2) 018 exchange in stereochemical studies to investigate the de novo polymerization of nucleotide diphosphate catalyzed by polynucleotide phosphorylase; 3) studies of the structural metal ion binding site on FBPase, the nature of the ligands at the site, the influence of the structural metal ion on substrate binding and the possibility that this site might be modified to exclude metal ion binding; 4) collaboration with G. Petsko at M.I.T. to carry out X-ray crystallographic studies on FBPase; and 5) initiation of series of mechanistic studies on restriction endonucleases commencing with the chemical synthesis of small, potential substrate molecules.